1. Field of the Invention
This invention relates to a process for making cyclodextrin complexes and, more particularly, to a method for forming a complex of cyclodextrin and a guest by precipitation.
2. Art Related to the Invention
Cyclodextrins, also called “Schardingers dextrins”, cycloamyloses, cyclomaltoses and cycloglucans, are oligomers of anhydroglucose, bonded together by alpha 1,4 bonds to form a ringed compound. A six membered ring is called alpha cyclodexrin; seven, beta cyclodextrin; and eight, gamma cyclodextrin. These six, seven and eight membered rings are also referred to as cyclomaltohexaose, cyclomaltoheptaose and cyclomaltooctaose, respectively.
Conventionally, cyclodextrins are obtained by treating a starch slurry with enzyme or acid to produce a gelatinized and liquefied slurry having a DE between 1 and 5. The gelatinized and liquefied starch slurry is then treated with cyclodextrin glycosyltransferase (CGT), at the appropriate pH, temperature and time for the selected CGT. The enzyme, CGT, is obtained from microorganisms such as Bacillus macerans, B. magaterium, B. circulans, B. stearothermohilus, and Bacillus sp. (alkalophilic) as well as others. The resulting digest from treatment of a gelatinized and liquefied starch slurry with CGT is then subjected to a separation and purification process to obtain cyclodextrins.
One of the commercially important aspects of cyclodextrins is their ability to form complexes with other chemical compounds. Physically, a cyclodextrin is donut-shaped. The interior of the donut is hydrophobic. The consequence of this is that cyclcodextrins are able to form inclusion complexes with substances that are less polar than water and have outer geometric dimensions corresponding to the diameter of the cyclodextrin cavity. Often the exterior of the cyclodextrin is modified to increase its hydrophilic nature. The cyclodextrin or modified cyclodextrin can be complexed with an insoluble or hydrophobic compound thereby forming a hydrophilic complex. In simple terms, this allows a compound insoluble in water to become soluble in water. The term “cyclodextrin” as used in the specification and claims means not only cyclodextrin per se but also modified cyclodextrins and branched cyclodextrins as well as combinations and mixtures thereof.
The most widely used method for forming a complex between a cyclodextrin and a guest molecule involves dissolving the cyclodextrin in water with a guest molecule and collecting the precipitate that forms. Conventionally, an aqueous solution of 10% (w/w) or less cyclodextrin is formed and then the guest is mixed into this solution. Mixing is continued and the resulting precipitate collected.
One of the problems with such a process is the large volume of water used to form a solution of guest molecule and cyclodextrin. This large volume of water creates processing problems and requires a filtration step to recovering the complex. Additionally, the precipitate typically had a large particle size which made it unfit for certain applications. It is generally recognized by those of skill in the art of cyclodextrins that precipitation is not a commercially viable method for making complexes.